The Neuropathology, Biomarker and Genetics Core C of this new National Institute of Neurological Disorders and Stroke (NINDS) Morris K. Udall Parkinson's Disease Research Center of Excellence (Udall Center) at the University of Pennsylvania School of Medicine (Penn) will acquire, preserve and characterize postmortem brain tissue in addition to biological samples collected antemortem from clinically assessed Parkinson's disease (PD) patients without and with cognitive impairments (CI), executive dysfunction and dementia (PDD) as well as dementia with Lewy body (DLB) patients and controls followed in Core B. PD, PDD and DLB represent a spectrum of overlapping neurodegenerative disorders known as alpha-synucleinopathies that are characterized by prominent filamentous alpha-synuclein (a-syn) aggregates mainly in neurons or their processes that are referred to as Lewy bodies (LBs) and Lewy neurites (LNs), respectively. Since emerging data suggest progression of PD/PDD/DLB could result from the cell-to-cell spread of pathological a-syn strains in the central nervous system followed by progressive neurodegeneration, efforts to understand the progression of PD to CI, executive dysfunction and dementia (Projects I/II) and mechanism of the cell-to- cell spread of pathological a-syn (Projects III/ IV) are the focus of the Penn Udall Center in the renewal period. Core C supports these goals by implementing postmortem diagnostic criteria for PD/PDD/DLB using state-of-the-art methods while also assessing the utility of other antemortem diagnostics including studies of potential PD/PDD/DLB biomarkers and molecular genetic strategies. Thus, Core C will work closely with the other Cores and all of the Projects in the Penn Udall Center to play a critical facilitative role in the mission of this Center by improving current diagnostic methods, and providing samples of thoroughly characterized fresh, unfixed frozen and fixed brain tissues as well as DNA and biofluids to investigators in this and other Udall Centers for research.